Abstract
BackgroundAberrant autophagy and preternatural elevated glycolysis are prevalent in bladder cancer (BLCA) and are both related to malignant progression. However, the regulatory relationship between autophagy and glycolytic metabolism remains largely unknown. We imitated starvation conditions in the tumour microenvironment and found significantly increased levels of autophagy and aerobic glycolysis, which both regulated the progression of BLCA cells. We further explored the regulatory relationships and mechanisms between them.MethodsWe used immunoblotting, immunofluorescence and transmission electron microscopy to detect autophagy levels in BLCA cells under different treatments. Lactate and glucose concentration detection demonstrated changes in glycolysis. The expression of lactate dehydrogenase A (LDHA) was detected at the transcriptional and translational levels and was also silenced by small interfering RNA, and the effects on malignant progression were further tested. The underlying mechanisms of signalling pathways were evaluated by western blot, immunofluorescence and immunoprecipitation assays.ResultsStarvation induced autophagy, regulated glycolysis by upregulating the expression of LDHA and caused progressive changes in BLCA cells. Mechanistically, after starvation, the ubiquitination modification of Axin1 increased, and Axin1 combined with P62 was further degraded by the autophagy–lysosome pathway. Liberated β-catenin nuclear translocation increased, binding with LEF1/TCF4 and promoting LDHA transcriptional expression. Additionally, high expression of LDHA was observed in cancer tissues and was positively related to progression.ConclusionOur study demonstrated that starvation-induced autophagy modulates glucose metabolic reprogramming by enhancing Axin1 degradation and β-catenin nuclear translocation in BLCA, which promotes the transcriptional expression of LDHA and further malignant progression.
Highlights
Bladder cancer (BLCA) is the second most common genitourinary tumour, with over 430,000 patients diagnosed worldwide per year [1]
This study aimed to investigate the connections between aberrant autophagy and enhanced aerobic glycolysis in bladder cancer (BLCA)
Treated groups were grown in Roswell Park Memorial Institute (RPMI) 1640 medium for T24 cells or Dulbecco’s modified Eagle’s medium (DMEM) for UM-UC-3 cells supplemented with 10% foetal bovine serum (Gibco, Thermo Fisher Scientific, MA)
Summary
Bladder cancer (BLCA) is the second most common genitourinary tumour, with over 430,000 patients diagnosed worldwide per year [1]. Autophagosomes fuse with lysosomes to form autophagic lysosomes for further degradation. This facilitates the cycling and reutilization of materials and energies [10,11,12]. It is known that cells require three main nutrients for survival, and under nutrient deprivation, cancer cells can reprogram their metabolic pathways. This is sometimes triggered by enhanced autophagy and leads to malignant progression [13, 14]. We imitated starvation conditions in the tumour microenvironment and found significantly increased levels of autophagy and aerobic glycolysis, which both regulated the progression of BLCA cells. We further explored the regulatory relationships and mechanisms between them
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
